Correlation between coronary artery calcification and COVID-19

Background: Coronary heart disease (CHD) is an underlying cardiac condition contributing to increased COVID-19 mortality and morbidity which can be assessed by several diagnosis methods including coronary artery calcification (CAC). The goal of this study was to find out if there were potential links between CAC, clinical findings, severity of COVID-19, and in-hospital outcomes. Methods: This retrospective study evaluated 551 suspected patients admitted to teaching hospitals of the Babol University of Medical Sciences, Babol, Iran, from March to October 2021. Data included previous diseases, comorbidities, clinical examinations, routine laboratory tests, demographic characteristics, duration of hospitalization, and number of days under ventilation were recorded in a checklist. Results: Findings of current study provide evidence of a significant relationship between coronary artery calcification (CAC) and in-hospital mortality. Additionally, we observed significant correlations between CAC and several clinical parameters including age, duration of hospitalization, pulse rate, maximum blood pressure, erythrocyte sedimentation rate (ESR), blood urea nitrogen (BUN), neutrophil count, white blood cell (WBC) count, and oxygen saturation. However, we did not observe a significant association between CAC and the severity index of COVID-19. In addition, logistic regression tests did not find a significant value of CAC to predict in-hospital mortality. Conclusion: Our findings showed a significant relationship between CAC and in-hospital mortality.

In 2019, a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic (1).CoVID-19 causes various symptoms, ranging from asymptomatic to severe pneumonia, acute respiratory distress syndrome (ARDS), and death (2).The COVID-19 infection has been associated with myocardial damage, acute heart failure, shock, and arrhythmia (3)(4)(5).Thirty percent of patients with COVID-19 exhibit cardiac complications (6).Some studies suggest that the severity of the respiratory syndrome and the risk of complications increase in patients with a history of cardiovascular disease (7).
Coronary heart disease (CHD) is one of the underlying cardiac conditions that has been suggested as a contributing factor to increasing COVID-19 mortality, which can be assessed by coronary artery calcification (CAC) (8,9).In a study, the presence of CAC on the chest computed tomography (CT) scan of hospitalized COVID-19 patients was linked to a less favorable prognosis (10).CAC may be associated with increased ventilation requirements, and death independent to age, and atherosclerotic heart disease (11).
However, further investigations are required to make a definite assumption.To create infection and enter to host cell, the SARS-CoV-2 virus needs to bind to the membrane receptor of angiotensin-converting enzyme 2 (ACE2) (12).In addition to other organs, the ACE2 receptor is also located in the heart (13).Consequently, cardiac complications of COVID-19 are prevalent, and potential associations between COVID-19 clinical outcomes and cardiovascular risk factors require discussion and investigation.
Although some studies have found relationships between cardiovascular diseases and COVID-19, the relationships between COVID-19 clinical outcomes and risk factors for cardiovascular diseases such as CAC and their measuring techniques are still under investigation.So, the goal of this study was to find out if there were potential links between CAC, clinical findings, COVID-19 severity, and the patient's in-hospital outcomes.

Methods
This retrospective study evaluated 551 suspected patients admitted to teaching hospitals of Babol University of Medical Sciences, Babol, Iran, from March to October 2021.Among the patients with suspected clinical symptoms of COVID-19 who were referred to the emergency department and underwent a chest CT scan or PCR, 551 patients with a confirmed diagnosis of COVID-19 were hospitalized and underwent further evaluation.
In this study, all hospitalized COVID-19 patients were enrolled if they were over 18 and given informed consent to participate in the study.If the patients had any of the following conditions, they were excluded from the study: 1. history of diseases that interfere with calcium deposition, such as malignancies, chronic kidney disease (CKD) or end stage renal disease (ESRD); 2. history of cardiovascular disease; 3. presence of connective tissue diseases; such as Marfan's syndrome and Ehlers-Danus; 4. any evidence for immunodeficiency; 5. and history of lung diseases.This research was reviewed and approved by the Research Ethics Committee of Babol University of Medical Sciences (Ethics approval number 724133341), and written informed consent was obtained from the subjects to include the clinical details.Individuals' personal information remained confidential during data collection, transfer, and storage.
First, information was recorded about the symptoms of infectious disease and the possible history of receiving treatment for it.All the information related to the previous diseases, comorbidities, and history of the patient's medications were obtained from their medical records and accompanying documents and recorded in a checklist.Also, clinical examinations and routine laboratory tests including CBC Diff, BUN, Cr, Na, K, PT, PTT, INR, ESR, CRP, AST, ALT, ALP were performed for all patients.Demographic characteristics such as age, sex, duration of hospitalization, O2 saturation levels, need for ventilation, as well as the number of days under ventilation, in addition to laboratory data including the level of procalcitonin, ESR, CRP, D-dimer, troponin, interleukin-6, BUN, and creatinine were evaluated and recorded in a checklist.CAC was assessed using a chest CT scan (Siemens emotion 16 slice, Germany) reported by a radiologist.SPSS Version 25 software was utilized to analyze data using t-test, ANOVA, chi-square, Spearman's correlation coefficient, and linear and logistic regression models.Results were reported using descriptive statistics, tables, and graphs.A p-value of less than 0.05 was considered significant.

Discussion
The goal of this study was to find out if there were potential links between CAC, clinical findings, COVID-19 severity, and in-hospital mortality.A significant relationship was found between CAC and in-hospital mortality, but our logistic regression test results did not find a significant value of CAC to predict in-hospital mortality.
Yogesh Sean Gupta et al. ( 14) conducted a similar study on 180 COVID-19 patients in 2021.Their results showed that CAC is significantly associated with intubation and inhospital mortality.Although we did not find any significant relationship between a need for ventilation and CAC, in line with their conclusions, our results showed a significant link between CAC and in-hospital mortality.
Anirudh Venugopalan Nair et al. ( 15) conducted a study on 67 patients to assess the potential relationships between CAC and COVID-19 clinical outcomes in Qatar in 2021.Their results demonstrated a significant relationship between CAC and in-hospital mortality, assisted ventilation, and ICU admission.Similarly, we also found significant relationships between CAC and mortality but did not find statistically significant relationships between CAC and ventilation or ICU admission.However, we found a significant link between the duration of hospitalization and CAC.These inconsistencies may be due to differences in CAC measurement techniques and our hospitals' limited ICU beds.
In contrast to our results, Leandro Slipczuk et al. ( 16) conducted a study on 493 patients, and in their regression models, they found that CAC can be an independent predictor of mortality.We did not find any significant value in CAC for predicting mortality.However, there was a significant relationship between them.In 2021, Elie Mousseaux et al. (17) investigated the potential links between CAC and COVID-19 6-month mortality in 169 patients.Their results showed a significant relationship between these variables.
Alberto Cereda et al. (18) investigated the possible links between gender, COVID-19 mortality, and CAC in 1683 patients.Their results showed that men had a significantly higher mortality rate and CAC than females.In contrast, we did not find significant relationships between gender and mortality.This could be due to the potential biases that occur when using a large sample size (19,20).
In Their results demonstrated a significant relationship between mortality and CAC, creatinine, and leukocyte count.Similarly, we found the same relationships.However, we did not investigate the possible links between creatinine and mortality.Instead, we assessed the relationship between BUN and mortality, which was statistically significant.One of the limitations of the present study is the absence of a control group.Additionally, conducting further studies with a larger sample size is recommended to investigate the relationship.
Our findings showed a significant relationship between CAC and in-hospital mortality.However, our logistic regression test results did not find a significant value of CAC to predict in-hospital mortality.CAC was also significantly related to age, duration of hospitalization, pulse rate, maximum blood pressure, ESR, BUN, neutrophil count, WBC count, and O2 saturation.However, it was not associated with the COVID-19 severity index.
2021, Philipp Fervers et al. (21) investigated the mortality prediction value of CAC (measured via the Agatston score) and other clinical variables in 89 patients.

Table 1 . Relationship between CAC with gender, in-hospital mortality, and ICU admission
*CAC: coronary artery calcification

Table 2 . Relationship between age, duration of hospitalization, and the number of days admitted to ICU with CAC
CAC: coronary artery calcification

Table 3 . Logistic regression test to predict the in-hospital mortality of patients with age, gender, and CAC control
CAC: coronary artery calcification

Table 4 . The relationship between CAC, and clinical and laboratory variables
CAC: coronary artery calcification

Table 5 . A summary of significant relationships found between CAC and some variables
CAC: coronary artery calcification